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HLA-A,-B,-C Alleles

Principle

Historically, HLA antigen determination relied on the lymphocytotoxicity assay. With the development of PCR-based methods and Next Generation Sequencing (NGS), DNA-based HLA typing has become the standard in modern clinical laboratories.

NGS provides ultra–high-resolution HLA typing by sequencing targeted regions of each HLA locus and matching the nucleotide data to the IMGT/HLA database. Compared with traditional methods such as SSO and SSP, NGS significantly reduces allele ambiguity and provides the most accurate and comprehensive genotyping available.

Clinically, HLA typing is essential for matching organ (e.g., kidney) and hematopoietic stem-cell transplant donors and recipients. Additionally, certain HLA alleles have well-established associations with immune response and disease susceptibility. The strongest example is HLA-B27, which is linked to ankylosing spondylitis, Reiter’s syndrome, and anterior uveitis. HLA sharing between partners has also been associated with recurrent pregnancy loss in some couples.

Specimen Requirements

Specimen

Whole blood

Collection

Lavender-top tubes (EDTA)

Storage and Transport

Send at room temperature

Minimum Volume

10 mL total (two 5 mL tubes)

Unacceptable Specimens

  • Clotted samples
  • Samples collected in a tube other than EDTA
  • Frozen specimens

Stability

Deliver to the laboratory within 72 hours

Method

Next Generation Sequencing (NGS)

Turnaround Time

10 business days

References

  • Terasaki PI, Bernoco F, Park MS, Ozturk G, Iwaki Y. Microdroplet testing for HLA-A, -B, -C, and -D antigens. Am J Clin Pathol. 1978;69:103–120.
  • Slater RD, Parham P. Mutually exclusive public epitopes of HLA-A, -B, -C molecules. Hum Immunol. 1989;26:85–89.
  • Bodmer J, Marsh S, Albert E, Bodmer W, et al. Nomenclature for factors of the HLA system, 1995. Hum Immunol. 1995;43:149–164.

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